Assisted hydrolysis of cis-2-(3-phenylthioureido)cyclo pentane-carbonitrile in alkaline solution. Solvent dependent switch from hydrolysis to rearrangement of the iminothiooxopyrimidine intermediate

The cis and trans isomers of 2-(3-phenylthioureido)cyclopentanecarbonitrile, 1 , and the respective carboxamides, 3 , and acids, 4 , have been prepared. Acid cyclization of both nitriles, faster with the cis isomer, gave the more stable cis-2-thiooxo-cyclopenta[d]pyrimidin-4-one, 7 . In base cis- 1...

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Veröffentlicht in:Canadian journal of chemistry 2000-01, Vol.78 (1), p.84-94
Hauptverfasser: Atay, Ergun, Blagoeva, Iva B, Chubb, Francis L, Edward, John T, Pojarlieff, Ivan G, Toteva, Maria M
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Sprache:eng
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Zusammenfassung:The cis and trans isomers of 2-(3-phenylthioureido)cyclopentanecarbonitrile, 1 , and the respective carboxamides, 3 , and acids, 4 , have been prepared. Acid cyclization of both nitriles, faster with the cis isomer, gave the more stable cis-2-thiooxo-cyclopenta[d]pyrimidin-4-one, 7 . In base cis- 1 formed the cis 4-imino-2-thiooxopyrimidine 2 which in aqueous alkali broke down via 3 to the acid 4 ; while in the presence of 66% acetonitrile 2 rearranged to the 4-phenyliminopyrimidine 5 to give as final product the thioureido acid 6 carrying no phenyl group. The 1 H NMR data for imino and phenylimino derivatives 2 and 5 showed strong bias for conformation A with 1-N pseudoaxial in the cyclopentane ring. Spectra of the E andZ isomers of the iminopyrimidine 2 under slow exchange could be recorded in DMSO-d 6 . The phenylimino tautomer of 5 is observed in CD 3 OD and in CDCl 3 with the E and Z isomers in a 1:1 ratio. In DMSO-d 6 the phenylamino tautomer 5a is also detected. The first process in aqueous KOH, the conversion of nitrile cis- 1 into the imino intermediate 2 , reaches an equilibrium which shifts towards the nitrile at higher alkalinities because of ionization of the phenylthioureido group (K e = [ 2 ]/[ 1 ] = 2.43 and pK AH = 12.74). The cyclization of 1 to 2 is first order in [OH - ] while the slower breakdown of 2 is pH independent. The latter is 10 4 times faster than the hydrolysis of acetonitrile evidencing substantial anchimeric assistance. The change in the reaction route towards the rearranged phenyliminopyrimidine 5 upon addition of acetonitrile can be caused by the lower dielectric constant favouring the elimination step leading to the intermediate isothiocyanate, and by increased activity of OH - accelerating the (presumably) second order elimination step as opposed to the pH-independent hydrolysis of the imino derivative 2 . Key words: anchimeric assistance, phenylthioureido nitriles, iminothiooxopyrimidine tautomers, alkaline hydrolysis, solvent effects.
ISSN:0008-4042
1480-3291
DOI:10.1139/v99-216